Natural and unnatural α-amino acids are essential building blocks for protein synthesis, and are also widely useful as components of medicinally active molecules and chiral catalysts (See e.g., Bhat, et al. Chemistry of Natural Products, Springer: Narosa, 2005, pp. 317-393; Wang et al., Expanding the genetic code, Angew. Chem., Int. Ed., 44, 34-66 (2005); Davie et al., Asymmetric catalysis mediated by synthetic peptides, Chem. Rev. 107, 5759-5812 (2007); and Helmchen et al., Phosphinooxazolines—a new class of versatile, modular P,N-ligands for asymmetric catalysis, Acc. Chem. Res. 33, 336-345 (2000)). The Strecker synthesis—the reaction of an imine or imine equivalent with hydrogen cyanide, followed by nitrile hydrolysis—is an especially versatile chemical method for the synthesis of racemic α-amino acids (See e.g., Block et al., The isolation and synthesis of the naturally occurring α-amino acids. Chem. Rev. 38, 501-571 (1946), Miller, S. L. Production of some organic compounds under possible primitive earth conditions, J. Am. Chem. Soc. 77, 2351-2361 (1955)). Asymmetric Strecker syntheses using stoichiometric chiral reagents have been applied successfully on gram-to-multi-kilogram scales to the preparation of enantiomerically enriched α-amino acids (See e.g., Harada, K. Asymmetric synthesis of α-amino acids by the Strecker synthesis, Nature 200, 1201 (1963); Kuethe et al. A concise synthesis of (S)—N-ethoxycarbonyl-α-methylvaline, J. Org. Chem. 72, 7469-7472 (2007); and Shu et al., Synthesis of enantiopure Fmoc-α-methylvaline, Org. Proc. Res. Dev. 12, 298-300 (2008)). In principle, Strecker syntheses employing sub-stoichiometric quantities of a chiral reagent may provide a practical alternative to these approaches, but the reported catalytic asymmetric methods have seen only limited use on preparative scales (e.g., >1 gram) (See Gröger et al. Catalytic enantioselective Strecker reactions and analogous syntheses, Chem. Rev. 103, 2795-2827 (2003); Merino et al., Organocatalyzed Strecker reactions, Tetrahedron 65, 1219-1234 (2009)).
The limited use of existing catalytic methodologies may be ascribed to several important practical drawbacks, including the relatively complex and precious nature of the catalysts, and to the requisite use of hazardous cyanide sources in the procedures. Thus, a need for new catalytic asymmetric methods for synthesizing enantiomerically enriched amino acids remains.